前列腺癌进展相关转录因子研究

doi:10.3969/j.issn.1673-8640.2023.09.003

摘要/Abstract

摘要：

目的对相关研究发现的46个前列腺癌差异表达蛋白的上游转录调控机制进行分析和探讨。方法采用GeneGo MetaCore软件和IPA软件对46个差异蛋白进行生物信息学分析，明确这些差异蛋白的转录因子调控网络。采用GEPIA2数据库分析鉴定出的转录因子的表达量及其对前列腺癌患者生存情况的影响。结果共鉴定出20个转录调控网络。按差异表达蛋白的富集度进行排序，筛选出居前6位的转录调控网络，分别由特化蛋白1（SP1）、p53、阴阳1（YY1）、雄激素受体（AR）、c-Myc和Slug 6个转录因子调控。Kaplan-Meier生存曲线分析结果显示，高表达p53的前列腺癌患者无病生存期和总生存期均长于低表达p53的患者（P值分别为0.047、0.019），低表达AR的前列腺癌患者无病生存期长于高表达AR的患者（P=0.023），其余4个转录因子对前列腺癌患者预后无影响（P>0.05）。IPA软件分析结果显示，SP1、p53、YY1、AR和c-Myc由表没食子儿茶素没食子酸酯（EGCG）、蛋白激酶B（AKT）1、成纤维细胞生长因子2（FGF2）、β-雌二醇调控。结论通过分析46个前列腺癌差异表达蛋白的转录调控网络，发现6个与前列腺癌相关的转录因子和4个上游调节分子，可为前列腺癌早期筛查和预后评估提供新的靶标。

关键词: 蛋白质组学, 转录因子, 转录调控, 前列腺癌

Abstract:

Objective To investigate the 46 differentially expressed proteins of upstream transcriptional regulation mechanism in prostate cancer. Methods GeneGo MetaCore software and IPA software were used to conduct bioinformatics analysis on differential proteins and clarify the transcriptional regulatory network of these differential proteins. GEPIA2 database was used to analyze the expression level of identified transcription factors and their impacts on the survival of prostate cancer patients. Results Totally，20 transcriptional regulatory networks were identified. According to the enrichment of differentially expressed proteins，the top 6 networks were screened out to be regulated by 6 transcription factors，specificity protein 1（SP1），p53，Yin-Yang 1（YY1），androgen receptor（AR），c-Myc and Slug. Kaplan-Meier survival curve analysis showed that prostate cancer patients with high expression of p53 had long disease-free survival and overall survival compared to patients with low expression of p53（P=0.047 and 0.019，respectively）. The disease-free survival of prostate cancer patients with low expression of AR was longer than that of patients with high expression of AR（P=0.023）. The other 4 transcription factors had no impact on the prognosis of prostate cancer patients（P>0.05）. IPA software analysis results showed that SP1，p53，YY1，AR and c-Myc were regulated by epigallocatechin gallate（EGCG），protein kinase B（AKT）1，fibroblast growth factor 2（FGF2） and beta-estradiol regulation. Conclusions By analyzing the transcriptional regulatory network of 46 prostate cancer differentially expressed proteins，6 transcription factors and 4 upstream regulatory molecules related to prostate cancer have been found，which can provide new targets for early screening and prognostic evaluation of prostate cancer.

Key words: Proteomics, Transcription factor, Transcription regulation, Prostate cancer

中图分类号:

R446.1

孙传玉, 赵晓君, 葛圣阳, 张扬. 前列腺癌进展相关转录因子研究[J]. 检验医学, 2023, 38(9): 818-824.

SUN Chuanyu, ZHAO Xiaojun, GE Shengyang, ZHANG Yang. Transcription factors in prostate cancer progression[J]. Laboratory Medicine, 2023, 38(9): 818-824.

图/表 6

参考文献 32

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蛋白编号	蛋白名称	肽段（95%）	116∶114^①
P62241	40S核糖体蛋白S8	2	1.53
P31943	异质核糖核蛋白H	3	2.17
P11021	GRP78^②	27	2.21
P09669	细胞色素C氧化酶6抗体	2	2.38
P10606	细胞色素c氧化酶亚单位5B，线粒体	7	2.70
P06576	ATP合酶β亚单位，线粒体	13	2.83
P38646	应激70蛋白，线粒体	11	2.91
P21810	二聚糖	19	2.97
P49411	延伸因子Tu，线粒体	6	3.02
P22314	泛素样修饰活化酶1	5	3.34
P13667	蛋白二硫化物异构酶A4	5	3.77
Q5SSJ5	异染色质蛋白1-结合蛋白3	5	4.06
P55327	肿瘤蛋白D52	3	4.25
Q99623	抗增殖蛋白2	3	4.57
P07237	蛋白质二硫化物异构酶	17	4.70
Q9NZN4	EH结构域蛋白2	2	5.55
P10809	HSP60^③，线粒体	25	5.97
P06748	核磷胺	10	7.94
Q15063	成骨细胞特异性因子2	13	9.12
Q00796	山梨醇脱氢酶	9	9.82

蛋白编号	蛋白名称	肽段（95%）	116∶114^①
P62241	40S核糖体蛋白S8	2	1.53
P31943	异质核糖核蛋白H	3	2.17
P11021	GRP78^②	27	2.21
P09669	细胞色素C氧化酶6抗体	2	2.38
P10606	细胞色素c氧化酶亚单位5B，线粒体	7	2.70
P06576	ATP合酶β亚单位，线粒体	13	2.83
P38646	应激70蛋白，线粒体	11	2.91
P21810	二聚糖	19	2.97
P49411	延伸因子Tu，线粒体	6	3.02
P22314	泛素样修饰活化酶1	5	3.34
P13667	蛋白二硫化物异构酶A4	5	3.77
Q5SSJ5	异染色质蛋白1-结合蛋白3	5	4.06
P55327	肿瘤蛋白D52	3	4.25
Q99623	抗增殖蛋白2	3	4.57
P07237	蛋白质二硫化物异构酶	17	4.70
Q9NZN4	EH结构域蛋白2	2	5.55
P10809	HSP60^③，线粒体	25	5.97
P06748	核磷胺	10	7.94
Q15063	成骨细胞特异性因子2	13	9.12
Q00796	山梨醇脱氢酶	9	9.82

蛋白编号	蛋白名称	肽段（95%）	116∶114
P17661	结蛋白	62	0.03
O95810	血清剥夺反应蛋白3	3	0.13
Q9BX66	SORBS1	18	0.18
P08670	波形蛋白	65	0.19
P51911	钙调蛋白-1	43	0.20
P04792	β-1热休克蛋白	15	0.22
P63267	γ-肠平滑肌肌动蛋白	191	0.24
Q969G5	蛋白激酶C δ结合蛋白	6	0.24
P12109	胶原蛋白α-1（Ⅵ）链	19	0.25
P11047	γ-1层黏连蛋白	9	0.28
O94875	SORBS2	2	0.32
P24821	肌腱蛋白	7	0.35
Q15942	Zyxin	4	0.35
Q9Y490	Talin-1	21	0.36
P02452	α-1（Ⅰ）链胶原蛋白	92	0.38
P18206	黏着斑蛋白	15	0.39
P20774	Mimecan	6	0.40
Q93052	脂肪瘤相关抗体	12	0.41
Q09666	神经细胞分化相关蛋白	62	0.42
P07585	核心蛋白聚糖	12	0.43
P98160	基底膜特异性硫酸乙酰肝素蛋白聚糖核心蛋白	17	0.44
P30086	磷脂酰乙醇胺结合蛋白1	7	0.47
P06396	凝溶胶蛋白	20	0.49
P12111	胶原蛋白α-3（Ⅵ）链	63	0.50
P01834	Ig κ链C区	4	0.54
P10909	簇集蛋白	3	0.54

蛋白编号	蛋白名称	肽段（95%）	116∶114
P17661	结蛋白	62	0.03
O95810	血清剥夺反应蛋白3	3	0.13
Q9BX66	SORBS1	18	0.18
P08670	波形蛋白	65	0.19
P51911	钙调蛋白-1	43	0.20
P04792	β-1热休克蛋白	15	0.22
P63267	γ-肠平滑肌肌动蛋白	191	0.24
Q969G5	蛋白激酶C δ结合蛋白	6	0.24
P12109	胶原蛋白α-1（Ⅵ）链	19	0.25
P11047	γ-1层黏连蛋白	9	0.28
O94875	SORBS2	2	0.32
P24821	肌腱蛋白	7	0.35
Q15942	Zyxin	4	0.35
Q9Y490	Talin-1	21	0.36
P02452	α-1（Ⅰ）链胶原蛋白	92	0.38
P18206	黏着斑蛋白	15	0.39
P20774	Mimecan	6	0.40
Q93052	脂肪瘤相关抗体	12	0.41
Q09666	神经细胞分化相关蛋白	62	0.42
P07585	核心蛋白聚糖	12	0.43
P98160	基底膜特异性硫酸乙酰肝素蛋白聚糖核心蛋白	17	0.44
P30086	磷脂酰乙醇胺结合蛋白1	7	0.47
P06396	凝溶胶蛋白	20	0.49
P12111	胶原蛋白α-3（Ⅵ）链	63	0.50
P01834	Ig κ链C区	4	0.54
P10909	簇集蛋白	3	0.54

序号	转录因子	GO富集生物过程	总节点数/个	根节点数/个	P值
1	SP1	细胞组分转移、细胞黏附调控、生物特性调控	19	18	9.23×10^-57
2	p53	细胞凋亡的负调控	11	10	4.70×10^-31
3	YY1	细胞、器官发育、生物过程的负调控，细胞黏附的负调控	10	9	6.55×10^-28
4	AR	细胞凋亡负调控，抑制细胞增殖	8	7	1.14×10^-21
5	c-Myc	细胞凋亡负调控，Caspase^②活性调节	8	7	1.14×10^-21
6	Slug	生物过程的负调节，参与氧化应激反应	48	28	1.12×10^-78